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The short-term behavioral sequelae of neonatal jaundice treated with phototherapy
INFANT llEHAVIOR AND DEVELOPMENT 5, 289-299 0982)
The Sh0rt-Term Behavi0ral Sequelae of Neonatal Jaundice Treated with Ph0t0therapy* CHARLES A. NELSON AND FRANCES D E G E N H O R O W I T Z Department of Human Development University of Kansas Lawrence, KA 66045 To observe the short-term behavioral sequelae of neonatal jaundice (hyperbilirubinemia) and phototherapy using a before and after design, the Neonatal Behavioral AssessmentScale with Kansas supplements(NBAS-K) was administered to a group of jaundiced infants treated with phototherapy, and to an untreated comparison group immediately preceding phototherapy treatment, immediately following treatment, and at 2 weeks. The data were analyzed using a Repeated Measures Analysis of Variance computed on the individual test items (n = 36). The behavioral sequelae of treating moderate hyperbilirubinemia with phototherapy were not severe, although at 2 weeks of age the comparison infants scored higher than the treated infants on items dealing with state control and orientation. Many of the observed differences involved "modal" rather than "best" scores. The findings address the need to describe treated infants' typical behavior, and passible avenues of future research are discussed.
" ' P h y s i o l o g i c " j a u n d i c e o f the n e w b o r n is p r e s e n t in t h e first f e w d a y s o f life in as m a n y as 5 0 % o f all f u l l - t e r m i n f a n t s a n d 8 0 % o f all p r e - t e r m i n f a n t s ( L a n s k o w s k y , 1975; M a i s e l s , 1975). T h e p r e s e n c e o f j a u n d i c e is d e t e r m i n e d b y e l e v a t e d l e v e l s o f s e r u m b i l i r u b i n , a n e n d p r o d u c t o f t h e . c a t a b o l i s m o f h e m e . In m o s t c a s e s , b i l i r u b i n is n o r m a l l y m e t a b o l i z e d a n d e x c r e t e d w i t h o u t h a r m to t h e i n f a n t . H o w e v e r , n o t all i n f a n t s are e f f i c i e n t in this p r o c e s s a n d i f b i l i r u b i n a c c u m u l a t i o n is n o t e x c r e t e d it c a n b e c o m e i n c r e a s i n g l y t o x i c , r e s u l t i n g in k e r n i c t e r u s . K e r n i c t e r u s g e n e r a l l y o c curs w h e n c o n c e n t r a t i o n s o f b i l i r u b i n e x c e e d 2 0 to 2 5 m g p e r 100 m l ( a l t h o u g h t h e r e are d o c u m e n t e d c a s e s w h e r e it h a s b e e n less), a n d m a y b e c h a r a c t e r i z e d b y p o o r * This research was supported i~ part by the NationalInstituteof Child Healthand HumanDevelopmentin a grant to the second author (HD 5 ROI 10608), in part by the Bureau of the Education of the Handicapped (BEH) through the Institute for Early Childhood Research at the Universityof Kansas (USOE 300-77-0308), and in part by the National Institute of Child Health and Human Development in a predoctoral traineeship to the fast author (HE) IT32 07173). The authors would like to thank Mimi Aangenberg, Karen Barnes, Joseph Byrn¢, Vicki Czemicki, Ed Gaddis, Pat Linn, Jane McNally, Cindy Ryan, Chris Smith, Beth Stella, and Joseph Sullivan for their help in data collection, Madelyn Moss for arrangingtest times and testingsubjects, and Ellen Ganon for her editorial assistance. The statistical and computationaladvice of Judith Short-Franklinand Joe Lueke is also gratefully acknowledged. We are indebted to Vernon Branson, HelenGilles, and Charles Loveland, and the nursing staff at Lawrence Memorial Hospital, where the study was conducted, for their immense cooperation, and to the parents and infants who participated in the study. Reprint requests shouldbe sent to CharlesA. Nelson, Center for Researchin HumanI,earning, 205 Elliott Hall, 75 East River Road, Universityof Minnesota, Minneapolis, MN 55455. 289
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NELSON AND HOROWITZ
feeding, lethargy, depressed Moro Reflex, opisthotonic posturing, high tone hearing loss, ataxia, seizures, and choreoathetosis (Odell, Cukier, &. Maylalung, 1976; Telzrow, Snyder, Tronick, Als, & Brazelton, 1977). If not treated, the disorder can result in mental retardation or death. Because of this, hyperbilirubinemia of the newborn and the attendant risk of kernieterus remains a major problem in neonatal nurseries. The purpose of treating hyperbilirubinemia is to prevent kernicterus from developing. The most frequently used current method of treatment is phototherapy (Gartner & Lee, 1977), which is used in 96% of all U.S. hospitals delivering more than 2,000 babies per year (Maisels, 1975). In the hospital nursery that was the site of the present study, phototherapy involves completely undressing the infant and covering the infant's eyes. Infants are then placed in an open bassinet and positioned under a portable phototherapy unit, approximately 45.72 cm (18 inches) from the "bili" lights. The lights themselves consist of 10 20-watt, white fluorescent lights (Model: f20+ 12CW: light range = 300-700 nm) changed every 200 hours. Infants are rotated every few hours from a supine to a prone position and feeding often takes place under the lights. The present investigation attempted to explore the short-term behavioral sequelae in infants with hyperbilirubinemia treated with phototherapy. No attempt was made to separate experimentally the possible effects of jaundice independent of phototherapy treatment, for two reasons. First, to examine the independent effects of jaundice and phototherapy, we would have had to use a group of infants with jaundice who were not treated and a group of unjaundiced infants who were treated. Because the site of the present s t u ~ generally administers phototherapy treatment to all infants with bilirubin levels in excess of 13 or 14 mg%, no such control groups were available for our study. Second, because the constellation of jaundice combined with phototherapy is the common situation in American hospitals, our results would more accurately represent the effects that might be found in the vast majority of infants suffering from hyperbilirubinemia. Our only "control group," therefore, was comprised of matched normal infants who had no hyperbilirubinemia and thus did not receive phototherapy. Our major concern was simply to describe the developmental course of these tw6 groups over time. However, if our results showed severe behavioral consequences of the combined conditions of hyperbilirubinemia and phototherapy in comparison with normal, untreated infants, then the reasons for experimentally separating tTeatment conditions in'relation to jaundice would become more compelling. The research on the behavioral sequelae of phototherapy and bilirubin has not been extensive. Telzrow, Sriyder, Tronick, Als, and Brazelton (1980) recently compared jaundiced infants treat6d With phototherapy with a group of untreated, normal controls. The Neonatal Behavioral Assessment Scale (NBAS) was administered to both groups before and during treatment (days 3 and 6 respectively), and at I0 days of age. The authors reported group differences primarily on the orientation items (e.g., the ability to track the examiner's face from side to side) on all three days, with the most pronounced effects occurring during treatment (day 6). It
EFFECTSOF JAUNDICE AND PHOTOTHERAPY
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should be noted, however, that the testers administering the exams were not blind to condition (i.e., whether or not the infant was a treaiment or control subject),. In addition, because all three tests were done over a seven day period, it was not clear if the groups developed differently over this relatively short period of time, or if the groups simply differed on several test items (without regard to the origin of these differences). Further, because the second exam was actually done during treatment, it is difficult to describe the possible behavioral effects of phototherapy immediately following treatment. Thus, while the results reported by Telzrow et al. are important, they must nevertheless be considered tentative pending further research. In the present investigation, we were particularly interested in describing the developmental course of infants treated with phototherapy over the first 2 weeks of life and how this course would compare with a group of normal, untreated infants. We were further interested in exploring the use of modal scoring as employed in the NBAS-K to detect differences in behavior in a clinical population. To accomplish these goals, jaundiced infants treated with phototherapy were compared to a comparison group three times during the first month of life with the Neonatal Behavioral Assessment Scale (Brazelton, 1973) modified by the Kansas supplements (NBASK: Horowitz, Sullivan, & Linn, 1978). METHOD
Subjects Twenty-two infants born in Lawrence Memorial Hospital, Lawrence, Kansas, and who were full-term, of appropriate birthweight, and free of medical complications at birth were evaluated. The peak total-acting level of bilirubin in the treatment group averaged 13.8 mg per 100 ml (SD = 1.8, range = 11.2 to 16.5). The average level at which infants were placed under the lights was 13.0 mg% (SD = 1.6, range = 10.5 to 15.3), while the average level when the infants were removed was 9.3 mg% (SD = 2.1, range = 5 to 13.2). These averages included one subject who was treated twice. Eleven normal infants, m a t c h e d t o the treatment subjects on the dimensions specified below, served as comparison subjects. Only one of the treatment infants and one of the comparison infants were not Caucasian (Chinese and Japanese, respectively). Table 1 providesthe relevant background information for all subjects.
Design To reduce the likelihood that factors other than jaundice and phototherapy would contribute to the results, a matched control design was employed. A trealment subject entered the study once the physician's decision to implement phototherapy was reached. After the infant was identified, an appropriate comparison subject was chosen. An attempt was made to match infants on birthweight (__.400 grams), one and five minute Apgar scores (±1 point), mother's age ( ± 5 years), mother's education ( ± 2 years of schooling), father's age (___ 5 years), father's education ( _
292
NELSON AND HOROWlTZ TABLE 1 Background Information N=11
Variable
Treatment M
Birthweight (gm) Weight at Test I (gm) Mother's Age (yr) Mother's Education Father's Age (yr) Father's Education Race Type of Delivery Length of Labor (hrs) Grovida Para 1 Minute Apgar 5 Minute Apgar Baby's Age, TEST 1 (hrs) TEST 2 (hrs) TEST 3 (days) TEST 4 (days) Test Duration, TEST 1 (min) TEST 2 (min) TEST 3 (min) TEST 4 (min) Sex, Moles Females
Control SD
M
SD
3735 477. 48 3564.73 425.67 28.55 5.16 approx. 3 years college
3502 586.33 3400 550.74 24.73 3.17 approx. 3 years college
30.73 4.86 approx. 3 years college 13 Caucasian, 1 Chinese 11 Span. Vaginal, 3 C-S * 9.22 3.11 2.27 1.0 1.82 1.01 8.37 .67 9.9 .30 62.09 17.62 137.93 16.75 14.27 I. 10 28.0 0.0 27.27 4.67 29.73 8.36 25.27 4.22 29.16 8.61 7 4
26.01 3.0 approx. 3 years college 13 Caucasian, 1 Japanese 11 Span. Vaginal, 3 C-S 9.27 6.02 2.09 .83 1.82 .87 8.63 .92 9.73 .47 55.36 14.24 141.43 22.42 14.91 1.92 29.33 2.34 28.18 6.81 30.09 10.91 21.64 4.48 21.00 4.18 8 3
o C-S = Caesarian Section.
2 years of schooling), approximate medication level, ~ race, type of delivery, and age at time of testing ( _ 18 hours; see Table 1). Procedure The treatment group infants were tested as soon as possible after treatment was prescribed. This resulted in the initial test being given just before or just after the onset of phototherapy. Thus, referring to the initial exam as " b e f o r e " treatment means either completely before treatment was begun or before the major portion of treatment occurred. The remainder of the exams occurred immediately after off-set of phototherapy, and at 2 weeks of age. For each treated subject, a comparison subject was also tested three times, each time at approximately the same age that the matched treatment infants had been tested (see Table 1). All infants were tested with the Brazelton Neonatal Behavioral Assessment Scale with Kansas Supplements Four levels of medication matching were involved: No m~lication, light medication (0 to 50 rag), moderate medication (51 to 100 mg), and heavy medication (101 to 150 rag). Excluding Caesarean sections, the following drugs were used in this sample: Atarax, Demeroi, Nembutal, Nisentil, Phenegran, Seconal, Sparine, Tborazine, Vistaril, Valium,, Morphine, Codeine, and "other" narcotics. Normal control infants were matched to the treated infant~; primarily on the basis of how much of the medications listed above were administered (i.e., level; none, light, moderate; and heavy).
EFFECTS OF JAUNDICE AND PHOTOTHERAPY
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(NBAS-K: Horowitz, Sullivan, & Linn, 1978) by reliable testers (N = 12), and all testers were "blind" to type of subject. In the cases where phototherapy had already begun before the initial exam, the nurse-coordinator at the Infant Research Laboratory, University of Kansas, and the newborn nursery staff at the hospital would "prepare" an infant for testing by removing the eye patches, diapering the infant, and placing the infant's bassinet among the others. Testers were not told at any time during the study if the infant was a treatment or comparison baby, or if in fact the infant was in the study at all (i.e., NBAS-K exams are done routinely at the hospital and frequently done at home in various follow-up research that is part of the Kansas Infant Research Laboratory Program). The presence of yellowish skin (a visual sign of jaundice) could have cued the testers. However, interviews conducted with the testers after the completion of the study revealed that skin coloration did not appear to arouse their suspicions that an infant was being tested because he or she was jaundiced. The initial and after-treatment examinations of the treatment group were conducted in the hospital, while the 2 week examinations were conducted in the infants' homes. For the comparison group, only the first was conducted in the hospital, with the majority of the remaining examinations being done at home because the matching on age determined when the exam had to he administered (i.e., most infants went home by day 3). Twenty-four treatment and 27 comparison infants originally entered the study. Due to subject attrition, missed exams, and inappropriate matching, only 14 treatment and 14 comparison subjects were evaluated at the first and second testing points. By 2 weeks the sample dropped to 11 .treatment and 11 comparison subjects. Subject loss over this period of time was generally due to missed examinations (because of the restriction imposed by matching age) and parental decision not to continue in the study, or unavailability for testing at the scheduled time. There was no pattern of one group of infants being withdrawn from the study more than the other. RESULTS To assess any differences that may have existed between the treatment and comparison infants on the matching background variables, t-tests for paired comparisons (Hays, 1973) were computed for each characteristic included in Table 1 (excluding education level of the parents, race, and type of delivery). The groups differed only with respect to the parents' age, with the treatment infants' mothers and fathers being slightly older (respectively, t (10) = 3.05, p < . 0 2 for mothers, and t (9) = 2.55, p < . 0 5 for fathers). Because of our interest in specific behavioral effects, the NBAS-K data were subjected to an item by item analysis. In order to investigate the pattern of change of the two groups over time, a Repeated Measures Analysis of Variance was computed. on 36 items (Subject x Item x Test). Excluded from the analysis due to incomplete or missing data were the reflex and decrement items. Of the 36 items analyzed, 20 were statistically significant. The nonorientation items in which a main effect or an interaction effect was significant are
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NELSON AND HOROWlTZ
displayed in Figure I, while similar findings for the orientation items are displayed in Figure 2. In the data displayed'in Figure 1, main effects of Test were found for alertness (F = 6.60, p<.003), peak of excitement (F = 4.08, p<'.025), skin color (F = 3.43, p < .04), self-quieting (F = 5.56, p<.007), hand to mouth activity (F = 5.90, p <.006), quality of responsiveness (F = 8.36, p <.001 ), examiner persistence (F = 9.18, p<.001), general irritability (F = 7.25, p<.002), and reinforcement value (F = 8.24, p < .001). In addition, there was a main effect of Group for activity level (F = 6.99, p < . 0 2 ) and quality of responsiveness (F = 5.91, p<.025), with the treatment infants being judged overall as less active and lower in quality of responsiveness, and a Test x Group interaction of lability of state (F = 3.39, p < . 0 4 ) and general irritability (F = 5.60, p<.007). Duncan's Multiple Range Test (Keppel, 1973) was used to analyze the source of the interaction for lability of state and general irritability. The results revealed that the treatment infants manifested more state changes than the comparison infants at 2 weeks (p<.05), but the groups performed comparably otherwise. Furthermore, the treatment group was less irritable than the comparison group immediately after treatment (Test 2; p < . 0 5 ) but more irritable at 2 weeks (Test 3; p<.05). The overall significant Test effects suggest that the pattern' of change for these items over the first 2 weeks of life was similar in both groups. There was some indication from inspection of Figure 1 that the comparison infants were consistently judged to be more alert, be more reinforcing to the examiner, and show less self-quieting behavior and less hand to mouth activity than the treatment infants. However, the lack of a significant Test x Group interaction prevented further analyses of these differences. The significant main effect of Group for activity level indicated that the comparison infants scored higher, overall, than the treated infants, while the significant main effect of Test and of Group for quality of responsiveness indicated that the comparison infants performed higher than the treated infants, with the pattern of change over time in both groups being the same. The significant Test x Group interaction for lability of state and general irritability permitted us to conclude that infants' scores on these items varied across test as a function of group membership. While both the treatment and comparison groups showed a comparable number of state changes both immediately before and after treatment, the comparison infants showed significantly fewer state changes at 2 weeks (Test 3). With respect to general irritability, there was no statistically significant difference between the groups at Test 1, but by Test 2 the treatment infants were less irritable than the comparison infants. This trend reversed, however, by Test 3 (2 weeks), with the comparison infants now being less irritable. In summary, it appears that the non-orientation items reaching significance cluster around a state control-interactive dimension. The two groups developed in similar ways on this dimension through 2 weeks, although there was some indication that the comparison infants performed consistently higher than the treatment infants on quality of responsiveness, and that at 2 weeks these same infants were also less irritable and manifested fewer state changes.
295
EFFECTS OF JAUNDICE AND PHOTOTHERAPY Examiner Persistence
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Figure 1. Resultsof the Repeated Measures Analysis of Variance for the nan-orientation items.
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NELSON AND HOROWlTZ
It might be predicted from the results reviewed above that infants who are more responsive to the testing situation, who demonstrate greater state control, and who are generally less irritable, might also score higher on the orientation items, particularly at 2 weeks. The results of the analysis perforined on the orientation items for Tests I through 3 are relevant to this question. Mean performances on each of the orientation items are shown in Figure 2. Analyses of these means revealed a main effect of Test for inanimate visual, Best (F = 6.04, p < . 0 0 5 ) , inanimate auditory, Best (F = 3.42, p < . 0 4 ) , animate auditory, Best (F = 5.04, p < . 0 1 ) , inanimate visual, Modal (F = 3.87, p < . 0 3 ) , inanimate auditory, Modal (F = 6.53, p<.004), animate visual, Modal (F = 3 . 3 5 , p < . 0 5 ) , and animate visual and auditory, Modal (F = 3.44, p<.04). A main effect of Group was found for animate auditory, Best (F = 4.79, p < . 0 4 ) and animate auditory, Modal (F = 12.57, p<.002), with the treatment infants performing more poorly overall than the comparison infants on both items. No interaction effects were found. The results of the analyses computed on the orientation items allow us to conclude that the overall Test effects describe a course of performance over the first 2 weeks of life that was not different for the two groups of subjects. On only two of these items (animate auditory, Best and Modal) did the comparison infants perform significantly higher than the treatment infants. However, as was noted for the trends on the non-orientation items, the direction of differences for the orientation items shown in Figure 2 was always in favor of stronger performance for the comparison subjects. In general, when the analysis computed on the orientation items is considered in conjunction with the similar analysis computed on the non-orientation items, it can be concluded that both groups followed a similar developmental course through 2 weeks of life, although at 2 weeks the comparison infants tended to manifest more state control and perform better on an interactive dimension than the treatment infants. Although the possible effects of bilirubin and phototherapy were not experimentally separated, a statistical attempt was made to assess the relative contributions of these factors as they might have affected the behavior of the treatment infants over the first 2 weeks of life. Partial correlations testing the relationship between the peak bilirubin level and NBAS-K scores and hours in treatment and NBAS-K scores were performed on the data resulting from each of the three test administrations (n = I I). However, few of these correlations exceeded chance or were interpretable, and therefore these results will not be discussed. DISCUSSION The results of the analysis of variance revealed a sizeable number of Test effects, but relatively few Group and Test x Group interaction effects. From these results one could conclude that jaundiced infants treated with phototherapy demonstrate a pattern of development through 2 weeks'of life that is not markedly different from a group of normal, untreated infants. -. Although there were relatively few iiems for which statistically significant
297
EFFECTSOF JAUNDICEAND PHOTOTHERAPY Inanimate V i s u a l , Best S
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Figure 2. Resultsof the RepeatedMeasuresAnalysisof Variancefor the orientation items.
298
NELSON AND HOROWITZ
results differentiated the two groups, we could not help but notice the interesting overall consistency of direction of differences at 2 weeks of age. We decided to test the significance of this observation by considering those items on the NBAS-K whereb~¢ a higher score clearly indicates stronger or more mature performance. Of the 24 items satisfying this criterion, the comparison infants performed better than the treatment infants on 19 items. Having better performance on 19 of 24 items was significant by a Chi-square analyses X2 (2) = 24.25, p <.01, even though on relatively few items were the group differences themselves significantly different. Thus, while the groups developed similarly through 2 weeks, item by item, the overall trend was in favor of the comparison infants. The items dealing with state control and interactive functioning contributed particularly to this trend. At 2 weeks the comparison infants were less irritable, manifested more state control, and were more responsive to the tester. There was also some suggestion from the items displayed in Figure 2 that these same infants also performed better On many of the orientation items, although a lack of significant Test x Group interactions pre-" vented a direct test of this assumption. It may be useful to speculate about the possible meaning of the behavioral differences observed in this study. Treated infants tended to be less reinforcing at 2 weeks than comparison infants. Lancioni, Horowitz, and Sullivan (1980) found that. at 2 we~eks of age infants who were judged as less likeable or less reinforcing were also scored as having a lower level of quality of responsiveness, required more examiner persistence, were more irritable, and performed poorer on the orientation items. Inspection of the data shown in Figures 1 and 2 reveal similar patterns of scores. Further, on the orientation items, particularly those involving responsivehess to animate stimulation, in this study it was the modal rather than the best performance in which a differential trend for the two groups was in evidence, with the treated infants showing poorer response to animate stimulation. Our group has speculated elsewhere (Horowitz, Sullivan, & Linn, 1978) that caregivers a/'e more likely to interact with the sample of behavior we call "modal" or typical than they are with the infant's "best" performance elicited by skilled NBAS-K testers. Thus, dt 2 weeks it is possible that the treated infants are less reinforcing to their caretakers and that a concomitant of that is evidenced in the typical kind of responses to animate (caregiver) stimulation provided the infant in caregiver-infant interactions. It would, therefore, be of interest in subsequent investigations tO explore these matters more fully by observing treatment infant interffctions with hospital staff and other caregivers. This would help establish how seriously we ought to take the significant and non-significant but consistent trends revealed in our data. The results of the present study partially concur with those reported by Telzrow et al. (1980). In both studies treated infants tended to perform more poorly than comparison infants on a state control/interactive dimension. Telzrow et al. observed this pattern to be most evident during treatment (day 6). We, however, observed that the treatment infants performed less well than the comparison infants on a state control/interactive dimension at 2 weeks, although the overall direction of differences definitely favored stronger and more mature performance among the
EFFECTS OF JAUNDICE AND: PHOTOTHERAPY
299
~.omparison infants. The sample was small ~nd the magnitude of differences in absolute terms not large. Thus, while it may be of interest in subsequent investigations to independently assess the effects of phototherapy and peak bilirubin, it seems equally important to gather data on other samples, to extend the assessment period beyond the first 2 weeks of life, and to investigate whether the trends in the observed differences can be shown to affect infant-caregiv~r interaction.
REFERENCES Brazeiton, T. B. Neonatalbehavioral assessment scale. London: Spastics International Medical Publications, 1973. Gartner, L. M., & Lee, K-S. Jaundice and liver disease. From R. E. Bellman (Ed.), Neonatalperinatal medicine. St. Louis, MO: C. V. Mosby, 1977. Hays, W. L. Statisticsfor the social sciences. New York: Holt, Rinehart, and Winst6rl, 1973. Horowitz, F. D., Sullivan, J. M., & Linn, P. A.. Stability and instability in the newbora infant: The quest for elusive threads. In A. J. Sameroff (Ed.), Organization and stability of newborn behavior: A commentary on the Brazelton Neonatal Behavior Assessment Scale. Monographs of the Society for Research in Child Development, 1978, 43, 29--45. Keppel, G. Design & analysis. Engiewood Cliffs, NJ: Prentice-Hall, 1973. Lancioni, G. E., Horowitz, F. D., & Sullivan, J. W. The NBAS-K: II. Reinforcement value of the infant's behavior. Infant Behavior and Development, 1980, 3,361-366. Lanzkowsky, P. Thejaundiced newborn: Causes and importance. Paper presented at the Symposium on Hematologic Diseases in Children, New York, 1975. Lucey, J. F. Neonatal phototherapy, uses, problems, and questions. Seminars in Hematology, 1972, 9, 127. Maisels, M. M. Bilirnbin; on understanding and influencing its metabolisfft in the newborn irffant. Pediatric Clinics of North America, 1972, 19,447. Maisels, M. M. Neonatal jaundice. From G. B. Avery (Ed.), Neonatology: Pathaphysiology and managethent of the newborn. Philadelphia, PA: J. B. Lippincott, 1975. Odell, G. 1~., Cukier, J. O., & Maylalung, A. R. Pathogenesis of neonatal hyperbilirubinemia. From D. S. Young arid M. J. Hicks (Eds,), The neonate: Clinical biochemistry, physiology, and pathology. New York-: V~/iley, 1976. Scheidt, P. C., Mellits, E. El,, Hardy, J. B., Drage, J. S., & Boggs, T. R. Toxicity to bilirubin in neonates: Infant development during the fhst year in relation to maximum neonatal serum bilirubin concentration. Journal of Pediatrics, 1977, 91,292-297. Sameroff, A. J. Organization and stability of newborn behavior: A commentary on the Brazelton Neonatal Behavior Assessment Scale. Monographs of the Society for Research in Child Development, 1978, 43, Nos. 5-6. Telzrow, R. W., Snyder, D. M., Troniek, E., Ads, H., & Brazelton, T. B. The effects ofphatotherapy on neonatal behavior. Paper presented to the Society for Research in Child Development, New Oricans, March, 1977. Telzrow, R, W., Snyder, D. M., Tronick, E., Ads, HI, & Brazelton, T. B. The behavior ofjanndiced infants undergoing phototherapy. Developmental Medicine and Child Neurology, 1980, 22, 317-326.
The Sh0rt-Term Behavi0ral Sequelae of Neonatal Jaundice Treated with Ph0t0therapy* CHARLES A. NELSON AND FRANCES D E G E N H O R O W I T Z Department of Human Development University of Kansas Lawrence, KA 66045 To observe the short-term behavioral sequelae of neonatal jaundice (hyperbilirubinemia) and phototherapy using a before and after design, the Neonatal Behavioral AssessmentScale with Kansas supplements(NBAS-K) was administered to a group of jaundiced infants treated with phototherapy, and to an untreated comparison group immediately preceding phototherapy treatment, immediately following treatment, and at 2 weeks. The data were analyzed using a Repeated Measures Analysis of Variance computed on the individual test items (n = 36). The behavioral sequelae of treating moderate hyperbilirubinemia with phototherapy were not severe, although at 2 weeks of age the comparison infants scored higher than the treated infants on items dealing with state control and orientation. Many of the observed differences involved "modal" rather than "best" scores. The findings address the need to describe treated infants' typical behavior, and passible avenues of future research are discussed.
" ' P h y s i o l o g i c " j a u n d i c e o f the n e w b o r n is p r e s e n t in t h e first f e w d a y s o f life in as m a n y as 5 0 % o f all f u l l - t e r m i n f a n t s a n d 8 0 % o f all p r e - t e r m i n f a n t s ( L a n s k o w s k y , 1975; M a i s e l s , 1975). T h e p r e s e n c e o f j a u n d i c e is d e t e r m i n e d b y e l e v a t e d l e v e l s o f s e r u m b i l i r u b i n , a n e n d p r o d u c t o f t h e . c a t a b o l i s m o f h e m e . In m o s t c a s e s , b i l i r u b i n is n o r m a l l y m e t a b o l i z e d a n d e x c r e t e d w i t h o u t h a r m to t h e i n f a n t . H o w e v e r , n o t all i n f a n t s are e f f i c i e n t in this p r o c e s s a n d i f b i l i r u b i n a c c u m u l a t i o n is n o t e x c r e t e d it c a n b e c o m e i n c r e a s i n g l y t o x i c , r e s u l t i n g in k e r n i c t e r u s . K e r n i c t e r u s g e n e r a l l y o c curs w h e n c o n c e n t r a t i o n s o f b i l i r u b i n e x c e e d 2 0 to 2 5 m g p e r 100 m l ( a l t h o u g h t h e r e are d o c u m e n t e d c a s e s w h e r e it h a s b e e n less), a n d m a y b e c h a r a c t e r i z e d b y p o o r * This research was supported i~ part by the NationalInstituteof Child Healthand HumanDevelopmentin a grant to the second author (HD 5 ROI 10608), in part by the Bureau of the Education of the Handicapped (BEH) through the Institute for Early Childhood Research at the Universityof Kansas (USOE 300-77-0308), and in part by the National Institute of Child Health and Human Development in a predoctoral traineeship to the fast author (HE) IT32 07173). The authors would like to thank Mimi Aangenberg, Karen Barnes, Joseph Byrn¢, Vicki Czemicki, Ed Gaddis, Pat Linn, Jane McNally, Cindy Ryan, Chris Smith, Beth Stella, and Joseph Sullivan for their help in data collection, Madelyn Moss for arrangingtest times and testingsubjects, and Ellen Ganon for her editorial assistance. The statistical and computationaladvice of Judith Short-Franklinand Joe Lueke is also gratefully acknowledged. We are indebted to Vernon Branson, HelenGilles, and Charles Loveland, and the nursing staff at Lawrence Memorial Hospital, where the study was conducted, for their immense cooperation, and to the parents and infants who participated in the study. Reprint requests shouldbe sent to CharlesA. Nelson, Center for Researchin HumanI,earning, 205 Elliott Hall, 75 East River Road, Universityof Minnesota, Minneapolis, MN 55455. 289
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feeding, lethargy, depressed Moro Reflex, opisthotonic posturing, high tone hearing loss, ataxia, seizures, and choreoathetosis (Odell, Cukier, &. Maylalung, 1976; Telzrow, Snyder, Tronick, Als, & Brazelton, 1977). If not treated, the disorder can result in mental retardation or death. Because of this, hyperbilirubinemia of the newborn and the attendant risk of kernieterus remains a major problem in neonatal nurseries. The purpose of treating hyperbilirubinemia is to prevent kernicterus from developing. The most frequently used current method of treatment is phototherapy (Gartner & Lee, 1977), which is used in 96% of all U.S. hospitals delivering more than 2,000 babies per year (Maisels, 1975). In the hospital nursery that was the site of the present study, phototherapy involves completely undressing the infant and covering the infant's eyes. Infants are then placed in an open bassinet and positioned under a portable phototherapy unit, approximately 45.72 cm (18 inches) from the "bili" lights. The lights themselves consist of 10 20-watt, white fluorescent lights (Model: f20+ 12CW: light range = 300-700 nm) changed every 200 hours. Infants are rotated every few hours from a supine to a prone position and feeding often takes place under the lights. The present investigation attempted to explore the short-term behavioral sequelae in infants with hyperbilirubinemia treated with phototherapy. No attempt was made to separate experimentally the possible effects of jaundice independent of phototherapy treatment, for two reasons. First, to examine the independent effects of jaundice and phototherapy, we would have had to use a group of infants with jaundice who were not treated and a group of unjaundiced infants who were treated. Because the site of the present s t u ~ generally administers phototherapy treatment to all infants with bilirubin levels in excess of 13 or 14 mg%, no such control groups were available for our study. Second, because the constellation of jaundice combined with phototherapy is the common situation in American hospitals, our results would more accurately represent the effects that might be found in the vast majority of infants suffering from hyperbilirubinemia. Our only "control group," therefore, was comprised of matched normal infants who had no hyperbilirubinemia and thus did not receive phototherapy. Our major concern was simply to describe the developmental course of these tw6 groups over time. However, if our results showed severe behavioral consequences of the combined conditions of hyperbilirubinemia and phototherapy in comparison with normal, untreated infants, then the reasons for experimentally separating tTeatment conditions in'relation to jaundice would become more compelling. The research on the behavioral sequelae of phototherapy and bilirubin has not been extensive. Telzrow, Sriyder, Tronick, Als, and Brazelton (1980) recently compared jaundiced infants treat6d With phototherapy with a group of untreated, normal controls. The Neonatal Behavioral Assessment Scale (NBAS) was administered to both groups before and during treatment (days 3 and 6 respectively), and at I0 days of age. The authors reported group differences primarily on the orientation items (e.g., the ability to track the examiner's face from side to side) on all three days, with the most pronounced effects occurring during treatment (day 6). It
EFFECTSOF JAUNDICE AND PHOTOTHERAPY
291
should be noted, however, that the testers administering the exams were not blind to condition (i.e., whether or not the infant was a treaiment or control subject),. In addition, because all three tests were done over a seven day period, it was not clear if the groups developed differently over this relatively short period of time, or if the groups simply differed on several test items (without regard to the origin of these differences). Further, because the second exam was actually done during treatment, it is difficult to describe the possible behavioral effects of phototherapy immediately following treatment. Thus, while the results reported by Telzrow et al. are important, they must nevertheless be considered tentative pending further research. In the present investigation, we were particularly interested in describing the developmental course of infants treated with phototherapy over the first 2 weeks of life and how this course would compare with a group of normal, untreated infants. We were further interested in exploring the use of modal scoring as employed in the NBAS-K to detect differences in behavior in a clinical population. To accomplish these goals, jaundiced infants treated with phototherapy were compared to a comparison group three times during the first month of life with the Neonatal Behavioral Assessment Scale (Brazelton, 1973) modified by the Kansas supplements (NBASK: Horowitz, Sullivan, & Linn, 1978). METHOD
Subjects Twenty-two infants born in Lawrence Memorial Hospital, Lawrence, Kansas, and who were full-term, of appropriate birthweight, and free of medical complications at birth were evaluated. The peak total-acting level of bilirubin in the treatment group averaged 13.8 mg per 100 ml (SD = 1.8, range = 11.2 to 16.5). The average level at which infants were placed under the lights was 13.0 mg% (SD = 1.6, range = 10.5 to 15.3), while the average level when the infants were removed was 9.3 mg% (SD = 2.1, range = 5 to 13.2). These averages included one subject who was treated twice. Eleven normal infants, m a t c h e d t o the treatment subjects on the dimensions specified below, served as comparison subjects. Only one of the treatment infants and one of the comparison infants were not Caucasian (Chinese and Japanese, respectively). Table 1 providesthe relevant background information for all subjects.
Design To reduce the likelihood that factors other than jaundice and phototherapy would contribute to the results, a matched control design was employed. A trealment subject entered the study once the physician's decision to implement phototherapy was reached. After the infant was identified, an appropriate comparison subject was chosen. An attempt was made to match infants on birthweight (__.400 grams), one and five minute Apgar scores (±1 point), mother's age ( ± 5 years), mother's education ( ± 2 years of schooling), father's age (___ 5 years), father's education ( _
292
NELSON AND HOROWlTZ TABLE 1 Background Information N=11
Variable
Treatment M
Birthweight (gm) Weight at Test I (gm) Mother's Age (yr) Mother's Education Father's Age (yr) Father's Education Race Type of Delivery Length of Labor (hrs) Grovida Para 1 Minute Apgar 5 Minute Apgar Baby's Age, TEST 1 (hrs) TEST 2 (hrs) TEST 3 (days) TEST 4 (days) Test Duration, TEST 1 (min) TEST 2 (min) TEST 3 (min) TEST 4 (min) Sex, Moles Females
Control SD
M
SD
3735 477. 48 3564.73 425.67 28.55 5.16 approx. 3 years college
3502 586.33 3400 550.74 24.73 3.17 approx. 3 years college
30.73 4.86 approx. 3 years college 13 Caucasian, 1 Chinese 11 Span. Vaginal, 3 C-S * 9.22 3.11 2.27 1.0 1.82 1.01 8.37 .67 9.9 .30 62.09 17.62 137.93 16.75 14.27 I. 10 28.0 0.0 27.27 4.67 29.73 8.36 25.27 4.22 29.16 8.61 7 4
26.01 3.0 approx. 3 years college 13 Caucasian, 1 Japanese 11 Span. Vaginal, 3 C-S 9.27 6.02 2.09 .83 1.82 .87 8.63 .92 9.73 .47 55.36 14.24 141.43 22.42 14.91 1.92 29.33 2.34 28.18 6.81 30.09 10.91 21.64 4.48 21.00 4.18 8 3
o C-S = Caesarian Section.
2 years of schooling), approximate medication level, ~ race, type of delivery, and age at time of testing ( _ 18 hours; see Table 1). Procedure The treatment group infants were tested as soon as possible after treatment was prescribed. This resulted in the initial test being given just before or just after the onset of phototherapy. Thus, referring to the initial exam as " b e f o r e " treatment means either completely before treatment was begun or before the major portion of treatment occurred. The remainder of the exams occurred immediately after off-set of phototherapy, and at 2 weeks of age. For each treated subject, a comparison subject was also tested three times, each time at approximately the same age that the matched treatment infants had been tested (see Table 1). All infants were tested with the Brazelton Neonatal Behavioral Assessment Scale with Kansas Supplements Four levels of medication matching were involved: No m~lication, light medication (0 to 50 rag), moderate medication (51 to 100 mg), and heavy medication (101 to 150 rag). Excluding Caesarean sections, the following drugs were used in this sample: Atarax, Demeroi, Nembutal, Nisentil, Phenegran, Seconal, Sparine, Tborazine, Vistaril, Valium,, Morphine, Codeine, and "other" narcotics. Normal control infants were matched to the treated infant~; primarily on the basis of how much of the medications listed above were administered (i.e., level; none, light, moderate; and heavy).
EFFECTS OF JAUNDICE AND PHOTOTHERAPY
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(NBAS-K: Horowitz, Sullivan, & Linn, 1978) by reliable testers (N = 12), and all testers were "blind" to type of subject. In the cases where phototherapy had already begun before the initial exam, the nurse-coordinator at the Infant Research Laboratory, University of Kansas, and the newborn nursery staff at the hospital would "prepare" an infant for testing by removing the eye patches, diapering the infant, and placing the infant's bassinet among the others. Testers were not told at any time during the study if the infant was a treatment or comparison baby, or if in fact the infant was in the study at all (i.e., NBAS-K exams are done routinely at the hospital and frequently done at home in various follow-up research that is part of the Kansas Infant Research Laboratory Program). The presence of yellowish skin (a visual sign of jaundice) could have cued the testers. However, interviews conducted with the testers after the completion of the study revealed that skin coloration did not appear to arouse their suspicions that an infant was being tested because he or she was jaundiced. The initial and after-treatment examinations of the treatment group were conducted in the hospital, while the 2 week examinations were conducted in the infants' homes. For the comparison group, only the first was conducted in the hospital, with the majority of the remaining examinations being done at home because the matching on age determined when the exam had to he administered (i.e., most infants went home by day 3). Twenty-four treatment and 27 comparison infants originally entered the study. Due to subject attrition, missed exams, and inappropriate matching, only 14 treatment and 14 comparison subjects were evaluated at the first and second testing points. By 2 weeks the sample dropped to 11 .treatment and 11 comparison subjects. Subject loss over this period of time was generally due to missed examinations (because of the restriction imposed by matching age) and parental decision not to continue in the study, or unavailability for testing at the scheduled time. There was no pattern of one group of infants being withdrawn from the study more than the other. RESULTS To assess any differences that may have existed between the treatment and comparison infants on the matching background variables, t-tests for paired comparisons (Hays, 1973) were computed for each characteristic included in Table 1 (excluding education level of the parents, race, and type of delivery). The groups differed only with respect to the parents' age, with the treatment infants' mothers and fathers being slightly older (respectively, t (10) = 3.05, p < . 0 2 for mothers, and t (9) = 2.55, p < . 0 5 for fathers). Because of our interest in specific behavioral effects, the NBAS-K data were subjected to an item by item analysis. In order to investigate the pattern of change of the two groups over time, a Repeated Measures Analysis of Variance was computed. on 36 items (Subject x Item x Test). Excluded from the analysis due to incomplete or missing data were the reflex and decrement items. Of the 36 items analyzed, 20 were statistically significant. The nonorientation items in which a main effect or an interaction effect was significant are
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NELSON AND HOROWlTZ
displayed in Figure I, while similar findings for the orientation items are displayed in Figure 2. In the data displayed'in Figure 1, main effects of Test were found for alertness (F = 6.60, p<.003), peak of excitement (F = 4.08, p<'.025), skin color (F = 3.43, p < .04), self-quieting (F = 5.56, p<.007), hand to mouth activity (F = 5.90, p <.006), quality of responsiveness (F = 8.36, p <.001 ), examiner persistence (F = 9.18, p<.001), general irritability (F = 7.25, p<.002), and reinforcement value (F = 8.24, p < .001). In addition, there was a main effect of Group for activity level (F = 6.99, p < . 0 2 ) and quality of responsiveness (F = 5.91, p<.025), with the treatment infants being judged overall as less active and lower in quality of responsiveness, and a Test x Group interaction of lability of state (F = 3.39, p < . 0 4 ) and general irritability (F = 5.60, p<.007). Duncan's Multiple Range Test (Keppel, 1973) was used to analyze the source of the interaction for lability of state and general irritability. The results revealed that the treatment infants manifested more state changes than the comparison infants at 2 weeks (p<.05), but the groups performed comparably otherwise. Furthermore, the treatment group was less irritable than the comparison group immediately after treatment (Test 2; p < . 0 5 ) but more irritable at 2 weeks (Test 3; p<.05). The overall significant Test effects suggest that the pattern' of change for these items over the first 2 weeks of life was similar in both groups. There was some indication from inspection of Figure 1 that the comparison infants were consistently judged to be more alert, be more reinforcing to the examiner, and show less self-quieting behavior and less hand to mouth activity than the treatment infants. However, the lack of a significant Test x Group interaction prevented further analyses of these differences. The significant main effect of Group for activity level indicated that the comparison infants scored higher, overall, than the treated infants, while the significant main effect of Test and of Group for quality of responsiveness indicated that the comparison infants performed higher than the treated infants, with the pattern of change over time in both groups being the same. The significant Test x Group interaction for lability of state and general irritability permitted us to conclude that infants' scores on these items varied across test as a function of group membership. While both the treatment and comparison groups showed a comparable number of state changes both immediately before and after treatment, the comparison infants showed significantly fewer state changes at 2 weeks (Test 3). With respect to general irritability, there was no statistically significant difference between the groups at Test 1, but by Test 2 the treatment infants were less irritable than the comparison infants. This trend reversed, however, by Test 3 (2 weeks), with the comparison infants now being less irritable. In summary, it appears that the non-orientation items reaching significance cluster around a state control-interactive dimension. The two groups developed in similar ways on this dimension through 2 weeks, although there was some indication that the comparison infants performed consistently higher than the treatment infants on quality of responsiveness, and that at 2 weeks these same infants were also less irritable and manifested fewer state changes.
295
EFFECTS OF JAUNDICE AND PHOTOTHERAPY Examiner Persistence
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296
NELSON AND HOROWlTZ
It might be predicted from the results reviewed above that infants who are more responsive to the testing situation, who demonstrate greater state control, and who are generally less irritable, might also score higher on the orientation items, particularly at 2 weeks. The results of the analysis perforined on the orientation items for Tests I through 3 are relevant to this question. Mean performances on each of the orientation items are shown in Figure 2. Analyses of these means revealed a main effect of Test for inanimate visual, Best (F = 6.04, p < . 0 0 5 ) , inanimate auditory, Best (F = 3.42, p < . 0 4 ) , animate auditory, Best (F = 5.04, p < . 0 1 ) , inanimate visual, Modal (F = 3.87, p < . 0 3 ) , inanimate auditory, Modal (F = 6.53, p<.004), animate visual, Modal (F = 3 . 3 5 , p < . 0 5 ) , and animate visual and auditory, Modal (F = 3.44, p<.04). A main effect of Group was found for animate auditory, Best (F = 4.79, p < . 0 4 ) and animate auditory, Modal (F = 12.57, p<.002), with the treatment infants performing more poorly overall than the comparison infants on both items. No interaction effects were found. The results of the analyses computed on the orientation items allow us to conclude that the overall Test effects describe a course of performance over the first 2 weeks of life that was not different for the two groups of subjects. On only two of these items (animate auditory, Best and Modal) did the comparison infants perform significantly higher than the treatment infants. However, as was noted for the trends on the non-orientation items, the direction of differences for the orientation items shown in Figure 2 was always in favor of stronger performance for the comparison subjects. In general, when the analysis computed on the orientation items is considered in conjunction with the similar analysis computed on the non-orientation items, it can be concluded that both groups followed a similar developmental course through 2 weeks of life, although at 2 weeks the comparison infants tended to manifest more state control and perform better on an interactive dimension than the treatment infants. Although the possible effects of bilirubin and phototherapy were not experimentally separated, a statistical attempt was made to assess the relative contributions of these factors as they might have affected the behavior of the treatment infants over the first 2 weeks of life. Partial correlations testing the relationship between the peak bilirubin level and NBAS-K scores and hours in treatment and NBAS-K scores were performed on the data resulting from each of the three test administrations (n = I I). However, few of these correlations exceeded chance or were interpretable, and therefore these results will not be discussed. DISCUSSION The results of the analysis of variance revealed a sizeable number of Test effects, but relatively few Group and Test x Group interaction effects. From these results one could conclude that jaundiced infants treated with phototherapy demonstrate a pattern of development through 2 weeks'of life that is not markedly different from a group of normal, untreated infants. -. Although there were relatively few iiems for which statistically significant
297
EFFECTSOF JAUNDICEAND PHOTOTHERAPY Inanimate V i s u a l , Best S
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298
NELSON AND HOROWITZ
results differentiated the two groups, we could not help but notice the interesting overall consistency of direction of differences at 2 weeks of age. We decided to test the significance of this observation by considering those items on the NBAS-K whereb~¢ a higher score clearly indicates stronger or more mature performance. Of the 24 items satisfying this criterion, the comparison infants performed better than the treatment infants on 19 items. Having better performance on 19 of 24 items was significant by a Chi-square analyses X2 (2) = 24.25, p <.01, even though on relatively few items were the group differences themselves significantly different. Thus, while the groups developed similarly through 2 weeks, item by item, the overall trend was in favor of the comparison infants. The items dealing with state control and interactive functioning contributed particularly to this trend. At 2 weeks the comparison infants were less irritable, manifested more state control, and were more responsive to the tester. There was also some suggestion from the items displayed in Figure 2 that these same infants also performed better On many of the orientation items, although a lack of significant Test x Group interactions pre-" vented a direct test of this assumption. It may be useful to speculate about the possible meaning of the behavioral differences observed in this study. Treated infants tended to be less reinforcing at 2 weeks than comparison infants. Lancioni, Horowitz, and Sullivan (1980) found that. at 2 we~eks of age infants who were judged as less likeable or less reinforcing were also scored as having a lower level of quality of responsiveness, required more examiner persistence, were more irritable, and performed poorer on the orientation items. Inspection of the data shown in Figures 1 and 2 reveal similar patterns of scores. Further, on the orientation items, particularly those involving responsivehess to animate stimulation, in this study it was the modal rather than the best performance in which a differential trend for the two groups was in evidence, with the treated infants showing poorer response to animate stimulation. Our group has speculated elsewhere (Horowitz, Sullivan, & Linn, 1978) that caregivers a/'e more likely to interact with the sample of behavior we call "modal" or typical than they are with the infant's "best" performance elicited by skilled NBAS-K testers. Thus, dt 2 weeks it is possible that the treated infants are less reinforcing to their caretakers and that a concomitant of that is evidenced in the typical kind of responses to animate (caregiver) stimulation provided the infant in caregiver-infant interactions. It would, therefore, be of interest in subsequent investigations tO explore these matters more fully by observing treatment infant interffctions with hospital staff and other caregivers. This would help establish how seriously we ought to take the significant and non-significant but consistent trends revealed in our data. The results of the present study partially concur with those reported by Telzrow et al. (1980). In both studies treated infants tended to perform more poorly than comparison infants on a state control/interactive dimension. Telzrow et al. observed this pattern to be most evident during treatment (day 6). We, however, observed that the treatment infants performed less well than the comparison infants on a state control/interactive dimension at 2 weeks, although the overall direction of differences definitely favored stronger and more mature performance among the
EFFECTS OF JAUNDICE AND: PHOTOTHERAPY
299
~.omparison infants. The sample was small ~nd the magnitude of differences in absolute terms not large. Thus, while it may be of interest in subsequent investigations to independently assess the effects of phototherapy and peak bilirubin, it seems equally important to gather data on other samples, to extend the assessment period beyond the first 2 weeks of life, and to investigate whether the trends in the observed differences can be shown to affect infant-caregiv~r interaction.
REFERENCES Brazeiton, T. B. Neonatalbehavioral assessment scale. London: Spastics International Medical Publications, 1973. Gartner, L. M., & Lee, K-S. Jaundice and liver disease. From R. E. Bellman (Ed.), Neonatalperinatal medicine. St. Louis, MO: C. V. Mosby, 1977. Hays, W. L. Statisticsfor the social sciences. New York: Holt, Rinehart, and Winst6rl, 1973. Horowitz, F. D., Sullivan, J. M., & Linn, P. A.. Stability and instability in the newbora infant: The quest for elusive threads. In A. J. Sameroff (Ed.), Organization and stability of newborn behavior: A commentary on the Brazelton Neonatal Behavior Assessment Scale. Monographs of the Society for Research in Child Development, 1978, 43, 29--45. Keppel, G. Design & analysis. Engiewood Cliffs, NJ: Prentice-Hall, 1973. Lancioni, G. E., Horowitz, F. D., & Sullivan, J. W. The NBAS-K: II. Reinforcement value of the infant's behavior. Infant Behavior and Development, 1980, 3,361-366. Lanzkowsky, P. Thejaundiced newborn: Causes and importance. Paper presented at the Symposium on Hematologic Diseases in Children, New York, 1975. Lucey, J. F. Neonatal phototherapy, uses, problems, and questions. Seminars in Hematology, 1972, 9, 127. Maisels, M. M. Bilirnbin; on understanding and influencing its metabolisfft in the newborn irffant. Pediatric Clinics of North America, 1972, 19,447. Maisels, M. M. Neonatal jaundice. From G. B. Avery (Ed.), Neonatology: Pathaphysiology and managethent of the newborn. Philadelphia, PA: J. B. Lippincott, 1975. Odell, G. 1~., Cukier, J. O., & Maylalung, A. R. Pathogenesis of neonatal hyperbilirubinemia. From D. S. Young arid M. J. Hicks (Eds,), The neonate: Clinical biochemistry, physiology, and pathology. New York-: V~/iley, 1976. Scheidt, P. C., Mellits, E. El,, Hardy, J. B., Drage, J. S., & Boggs, T. R. Toxicity to bilirubin in neonates: Infant development during the fhst year in relation to maximum neonatal serum bilirubin concentration. Journal of Pediatrics, 1977, 91,292-297. Sameroff, A. J. Organization and stability of newborn behavior: A commentary on the Brazelton Neonatal Behavior Assessment Scale. Monographs of the Society for Research in Child Development, 1978, 43, Nos. 5-6. Telzrow, R. W., Snyder, D. M., Troniek, E., Ads, H., & Brazelton, T. B. The effects ofphatotherapy on neonatal behavior. Paper presented to the Society for Research in Child Development, New Oricans, March, 1977. Telzrow, R, W., Snyder, D. M., Tronick, E., Ads, HI, & Brazelton, T. B. The behavior ofjanndiced infants undergoing phototherapy. Developmental Medicine and Child Neurology, 1980, 22, 317-326.